DESCRIPTION: Recent investigations showed that electrical stimulation of vagal afferents affects nociception and putative pain modulatory neurons (On and OFF cells) in the rostroventral medulla in a manner opposite to what would be predicted based on the current hypothesis of ON-OFF cell function. The overall objective of the present proposal, therefore, is to perform electrophysiological studies that more selectively characterize the influence of vagal afferent activation on the activity of ON and OFF cells during periods of hypoalgesia and hyperalgesia. This will be accomplished by determining the effects of serotonin or serotonin receptor specific agonists/antagonists at doses that produce hypoalgesia and the effects of lipopolysaccarides at doses that produce hyperalgesia on the activity of ON and OFF cells in intact and vagotomized rats. In addition, all studies will include the recording of arterial blood pressure since the activity of ON and OFF cells is correlated to blood pressure, and some studies will include the recording of activity of lumbosacral spinothalamic tract cells to establish relationship between ON and OFF cell activity with the activity of spinal pain transmission neurons. The specific aims of this proposal are to (1) quantitatively characterize the influence and degree of vagal input to ON and OFF cells in the control of arterial blood pressure and the modulation of the nociceptive tail flick reflex, (2) quantitatively characterize the degree of somatic and visceral convergence to ON and OFF cells in the lightly and deeply barbiturate-anesthetized state, and (3) quantitatively characterize the spinopetal effects of ON and OFF cells on lumbosacral spinothalamic tract cells during activation of vagal afferents. These experiments will provide important information on the role of ON and OFF cells in spinopetal control of nociception, arterial blood pressure regulation, and visceral-visceral and visceral-somatic convergence.